1. Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats.
- Author
-
Filipović, Dragana, Novak, Božidar, Xiao, Jinqiu, Tadić, Predrag, and Turck, Christoph W.
- Subjects
PREFRONTAL cortex ,LIQUID chromatography-mass spectrometry ,SOCIAL isolation ,RAS proteins ,MACHINE learning ,G protein coupled receptors ,CALCIUM-binding proteins - Abstract
Chronic social isolation (CSIS) generates two stress-related phenotypes: resilience and susceptibility. However, the molecular mechanisms underlying CSIS resilience remain unclear. We identified altered proteome components and biochemical pathways and processes in the prefrontal cortex cytosolic fraction in CSIS-resilient rats compared to CSIS-susceptible and control rats using liquid chromatography coupled with tandem mass spectrometry followed by label-free quantification and STRING bioinformatics. A sucrose preference test was performed to distinguish rat phenotypes. Potential predictive proteins discriminating between the CSIS-resilient and CSIS-susceptible groups were identified using machine learning (ML) algorithms: support vector machine-based sequential feature selection and random forest-based feature importance scores. Predominantly, decreased levels of some glycolytic enzymes, G protein-coupled receptor proteins, the Ras subfamily of GTPases proteins, and antioxidant proteins were found in the CSIS-resilient vs. CSIS-susceptible groups. Altered levels of Gapdh, microtubular, cytoskeletal, and calcium-binding proteins were identified between the two phenotypes. Increased levels of proteins involved in GABA synthesis, the proteasome system, nitrogen metabolism, and chaperone-mediated protein folding were identified. Predictive proteins make CSIS-resilient vs. CSIS-susceptible groups linearly separable, whereby a 100% validation accuracy was achieved by ML models. The overall ratio of significantly up- and downregulated cytosolic proteins suggests adaptive cellular alterations as part of the stress-coping process specific for the CSIS-resilient phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF